IFNγ production during cell interactions distinguishes localized from diffuse pigmented villonodular synovitis and rheumatoid arthritis.

Abstract

Background: Pigmented villonodular synovitis (PVNS) is a rare articular disease characterized by aggressive synovial proliferation, with localized or diffuse forms. PVNS shares features of an inflammatory disease such as rheumatoid arthritis (RA), including immune cell infiltrate. Thus, we aimed to evaluate PVNS synoviocyte response to inflammatory stimulation or cell interactions to better understand their role in pathophysiology. Results were compared with those in RA.

Methods: Synoviocytes were treated with pro-inflammatory cytokines, IL-17 and/or TNF. IL-6 and IL-8 production was evaluated by ELISA in culture supernatants after 48 h. Migratory capacity was evaluated by a cell scraping assay. Peripheral blood mononuclear cells (PBMC) from healthy donors were co-cultured with PVNS or RA synoviocytes during 48 h, in the presence or not of phytohemagglutinin (PHA). Cytokine production (IL-17, IL-6, IFN-γ, IL-10, IL-1β and TNF) was measured by ELISA.

Results: The addition of IL-17 and TNF stimulated IL-6 and IL-8 secretion by both PVNS and RA synoviocytes, with similar responses between PVNS and RA synoviocytes. The highest production of IL-6 and IL-8 was obtained with the combination of IL-17 + TNF. Diffuse PVNS synoviocytes were less potent to cover a scratch area than localized PVNS or RA synoviocytes (p < 0.05). Finally, responses to cell interactions were assessed using co-cultures between synoviocytes and activated immune cells. IL-17, IL-6, IFNγ, IL-10, IL-1β and TNF production was measured after 48 h. Cell interactions induced massive cytokine production, mainly in PHA activated condition. The source of stromal cells affected the secretion resulting from these interactions. Localized and diffuse PVNS synoviocytes induced more IL-17 than RA synoviocytes (p ≤ 0.01). Localized PVNS induced more IFNγ than both diffuse PVNS and RA synoviocytes (p ≤ 0.05). IL-10 production was negatively correlated with IFNγ secretion.

Conclusion: In conclusion, results show differences in synoviocyte profiles or in response to cell interactions depending on synoviocyte source, with changes in IFNγ / IL-10 balance associated with localized PVNS. These differences could be used to adapt the therapeutic strategy to each form of PVNS.